Aldosterone antagonists. 3. Synthesis and activities of steroidal 7 alpha-(alkoxycarbonyl)-15,16-methylene spirolactones.
Several A- and D-ring substituted steroidal 7 alpha-alkoxycarbonyl spirolactones were synthesized with the purpose of increasing the aldosterone antagonistic potency and reducing the endocrinological side effects relative to the standard drug spironolactone. It was found that the 15 beta,16 beta-methylene derivative 17 exhibited a 2-fold higher aldosterone antagonistic activity compared to either spironolactone or the 15,16-unsubstituted derivative 29 while showing remarkably reduced antiandrogenicity.
Nickisch
K
K
Research Laboratories, Schering AG Berlin and Bergkamen, West Germany.
Bittler
D
D
Laurent
H
H
Losert
W
W
Nishino
Y
Y
Schillinger
E
E
Wiechert
R
R
D000818:Animals; D001681:Biological Assay; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D009919:Orchiectomy; D010060:Ovulation / Q000187:drug effects; D011245:Pregnadienes / Q000138:chemical synthesis* / Q000494:pharmacology; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000451:Mineralocorticoid Receptor Antagonists; D011245:Pregnadienes; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013148:Spironolactone; C054537:ZK 91587